ERKs and mitochondria-related pathways are essential for glycyrrhizic acid-mediated neuroprotection against glutamate-induced toxicity in differentiated PC12 cells

The present study focuses on the neuroprotective effect of glycyrrhizic acid (GA, a major compound separated from Glycyrrhiza Radix, which is a crude Chinese traditional drug) against glutamate-induced cytotoxicity in differentiated PC12 (DPC12) cells. The results showed that GA treatment improved cell viability and ameliorated abnormal glutamate-induced alterations in mitochondria in DPC12 cells. GA reversed glutamate-suppressed B-cell lymphoma 2 levels, inhibited glutamate-enhanced expressions of Bax and cleaved caspase 3, and reduced cytochrome C (Cyto C) release. Exposure to glutamate strongly inhibited phosphorylation of AKT (protein kinase B) and extracellular signal-regulated kinases (ERKs); however, GA pretreatment enhanced activation of ERKs but not AKT. The presence of PD98059 (a mitogen-activated protein/extracellular signal-regulated kinase kinase [MEK] inhibitor) but not LY294002 (a phosphoinositide 3-kinase [PI3K] inhibitor) diminished the potency of GA for improving viability of glutamate-exposed DPC12 cells. These results indicated that ERKs and mitochondria-related pathways are essential for the neuroprotective effect of GA against glutamate-induced toxicity in DPC12 cells. The present study provides experimental evidence supporting GA as a potential therapeutic agent for use in the treatment of neurodegenerative diseases.

The hypothesis of an effective strategy for resistance of hepatocellular carcinoma to therapy-autophagy / La hipótesis de una estrategia efectiva para la resistencia del carcinoma hepatocelular a la terapia autofágica

Hepatocellular carcinoma (HCC) is one of the most common malignant tumours and its five-year survival rate remains low. Autophagy is a catabolic process conserved among all eukaryotes ranging from yeast to mammals. Recently, many studies show that tumour cells can utilize autophagy as a cellular defence mechanism when facing metabolic stress. Thus, we hypothesize that autophagy may play an important role in the resistance of hepatocellular carcinomas to therapy. Although the exact role of autophagy on tumour cells is still complex and further studies are needed to prove the impact of autophagy on HCC, it suggests that autophagy may be a new therapeutic target for the resistance to therapy of HCC.

El carcinoma hepatocelular (CHC) es uno de los tumores malignos más comunes, y su tasa de super-vivencia a los cinco años sigue siendo baja. La autofagia es un proceso catabólico conservado en todos los eucariotas, que abarca desde las levaduras hasta los mamíferos. Recientemente, numerosos estudios han demostrado que las células tumorales pueden utilizar la autofagia como un mecanismo celular de defensa frente al estrés metabólico. De este modo, sostenemos la hipótesis de que la autofagia puede desempeñar un papel importante en la resistencia de los carcinomas hepatocelulares a la terapia. Aunque el papel exacto de la autofagia en las celulares tumorales sigue siendo complejo, y se requieren más estudios a fin de probar el impacto de la autofagia en el CHC, hay indicios de que la autofagia puede ser un nuevo objetivo terapéutico para la resistencia a la terapia del CHC.

Effect of hyperoxia on the intestinal IgA secretory component in neonatal rats and on intestinal epithelial cells in vitro

Oxygen therapy is essential for the treatment of some neonatal critical care conditions but its extrapulmonary effects have not been adequately investigated. We therefore studied the effects of various oxygen concentrations on intestinal epithelial cell function. In order to assess the effects of hyperoxia on the intestinal immunological barrier, we studied two physiological changes in neonatal rats exposed to hyperoxia: the change in intestinal IgA secretory component (SC, an important component of SIgA) and changes in intestinal epithelial cells. Immunohistochemistry and Western blot were used to detect changes in the intestinal tissue SC of neonatal rats. To detect intestinal epithelial cell growth, cells were counted, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Giemsa staining were used to assess cell survival. Immunohistochemistry was used to determine SC expression. The expression of intestinal SC in neonatal rats under hyperoxic conditions was notably increased compared with rats inhaling room air (P < 0.01). In vitro, 40 percent O2 was beneficial for cell growth. However, 60 percent O2 and 90 percent O2 induced rapid cell death. Also, 40 percent O2 induced expression of SC by intestinal epithelial cells, whereas 60 percent O2did not; however, 90 percent O2 limited the ability of intestinal epithelial cells to express SC. In vivo and in vitro, moderate hyperoxia brought about increases in intestinal SC. This would be expected to bring about an increase in intestinal SIgA. High levels of SC and SIgA would serve to benefit hyperoxia-exposed individuals by helping to maintain optimal conditions in the intestinal tract.

How we performed chest wall reconstruction: analysis 31 cases.

OBJECTIVE: To see the results of patients who underwent chest wall resection and reconstruction (CWRR). SETTING AND DESIGN: Retrospective descriptional study. MATERIAL AND METHODS: We retrospectively reviewed all patients who underwent CWRR at Xingtai People's Hospital in China and B.P. Koirala Memorial Cancer Hospital in Nepal. A total of 31 patients were reviewed. Among them, 20 were male and 11 female. The median age was 63 years. The indications for resection were primary chest wall tumor in 21 patients (67.7%), lung cancer with invasion of chest wall 6 (19.4%), recurrence of breast cancer 2(6.3%), radiation necrosis 1(3.2%) and skin cancer 1(3.2%). RESULTS: The mean number of rib resected was 3.6 ribs, which induced a mean defect of 97.1 cm2. Concomitant resection was done in 13 patients, including lung resection 10, partial resection of diaphragm 2, and partial sternectomy 1. Seven patients underwent soft tissue reconstruction (STR) alone and 5 patients skeletal reconstruction (SR) alone. Simultaneous SR and STR were performed in 19 patients. Three patients (9.7%) developed postoperative complications. The median survival period was 22 months. CONCLUSION: Primary chest wall tumor and lung cancer invading chest wall are the most common diseases indicating CWRR. Simultaneous bony and soft tissue reconstruction was reliable for chest wall reconstruction in most cases and prevents postoperative complications.

In vitro sensitivity of Plasmodium falciparum to eight antimalarials in China-Myanmar and China-Lao PDR border areas.

In 1991-1995 by using the Rieckmann in vitro micro-method, susceptibilities of Plasmodium falciparum to eight antimalarials in the China-Lao PDR and China-Myanmar border areas were tested. The resistant rates of P. falciparum to chloroquinine were 95.0%-100%; IC50 114-240nmol/l. P. falciparum resistant rates to amodiaquine resistance accounted for 83.5%-100%, IC50 52-72nmol/l. All cases were sensitive to quinine, IC50 470-608nmol/l. P. falciparum isolates from the Lao PDR frontier were highly sensitive to artesunate, dihydroartemisinin, and arteether. Resistant rates from other areas were 0-11%. P. falciparum from China-Myanmar and Lao PDR border areas were also sensitive to mefloquine, IC50 68-88nmol/l. A longitudinal survey of the sensitivity of P. falciparum in vivo on the China-Lao PDR border showed that the average defervescent time of falciparum malaria was treated by pyronaridine increased from 32.7 +/- 16.0 hours during 1984-85 to 56.2 +/- 27.4 hours in 1995; the recrudescence rate rose up from 15.2% to 37.5%. The results monitored in vitro showed that all cases assessed in 1988 for response to pyronaridine were sensitive, but 36.4% of cases had emerging resistance, IC50 increased from 13nmol/l to 40 nmol/l. The above results suggested that P. falciparum in these areas has expressed resistance to chloroquine and amodiaquine. However, the parasites are still sensitive to artemisinin, pyronaridine, mefloquine, quinine, but with a declining sensitivities.